Active Surveillance in Low- and Intermediate-Risk Prostate Cancer: Comparative Oncologic Safety, Patient Selection, and Predictors of Treatment Conversion in the Era of Multiparametric MRI: A Systematic Review and Meta-Analysis

Background/Objectives: Active surveillance (AS) is the preferred management strategy for localized low-risk prostate cancer. However, clinical debate persists regarding long-term oncologic safety beyond 10 years, the diagnostic reliability and false-negative risk of serial multiparametric MRI (mpMRI) for biopsy deferral, and the prognostic magnitude of adverse pathological patterns such as invasive cribriform morphology. This study aimed to provide a comprehensive meta-analytic synthesis of long-term oncologic survival, dynamic imaging performance, multivariable progression predictors, and longitudinal patient-reported functional outcomes. Methods: Registered with PROSPERO (CRD420261479059) and conducted per PRISMA 2020 and GRADE guidelines, electronic searches were performed across PubMed/MEDLINE, Web of Science, Scopus, and Cochrane CENTRAL through January 2026. Twenty-nine prospective cohorts, randomized trials, and diagnostic imaging studies comprising 46,318 patients were included. Time-to-event survival outcomes were synthesized using Generalized Linear Mixed Models (GLMMs) and random-effects inverse-variance models (REML). Diagnostic accuracy of serial mpMRI was modeled via bivariate random-effects meta-analysis (Reitsma approach). Multivariable-adjusted hazard ratios (aHRs) and longitudinal EPIC-26 domain scores were quantitatively pooled. Results: Across 10 cohorts reporting long-term outcomes (N = 24,987), pooled 10-year prostate cancer-specific survival (PCSS) was 98.9% (95% CI: 98.4–99.4%), demonstrating comparable oncologic efficacy to radical therapy. Pooled 10-year metastasis-free survival (MFS) was 96.2% (95% CI: 94.7–97.4%), and 10-year treatment-free survival (TFS) was 54.2% (95% CI: 48.1–60.3%; 95% prediction interval: 31.4–75.8%; I2 = 88.1%). Serial mpMRI demonstrated a pooled sensitivity of 85.6% (95% CI: 74.2–92.6%) and a negative predictive value of 93.4% (95% CI: 89.1–96.3%) for PRECISE 1–3, supporting selective biopsy deferral while recognizing a 6.6% residual risk of missed occult high-grade disease. Invasive cribriform morphology in Grade Group 2 was the strongest independent multivariable predictor of progression (aHR: 12.67, 95% CI: 4.77–33.64; two studies, 1420 patients, 184 progression events). AS preserved baseline urinary continence (+3.0 points at 12 months) and sexual function (−2.0 points at 12 months) compared to profound declines observed after radical prostatectomy (−17.0 and −35.0 points, respectively). Conclusions: Active surveillance provides comparable 10-year oncologic safety to immediate radical therapy while robustly preserving quality of life. Sequential mpMRI facilitates selective biopsy deferral, though invasive cribriform histology and visible target lesions indicate aggressive disease phenotypes that require proactive definitive intervention.